Mitochondrial DNA topoisomerase I (TOP1MT) (TOP1MT)

Mitochondrial DNA topoisomerase I (TOP1MT) is a nuclear-encoded enzyme specifically localized to the mitochondria, where it manages the topological state of mitochondrial DNA (mtDNA). It functions by creating transient single-strand breaks to relax supercoiled DNA, a process essential for mtDNA replication and transcription. The cleavage complex refers to the intermediate state where the enzyme is covalently bound to the DNA. Certain chemotherapeutic agents, such as camptothecin derivatives, stabilize this complex, preventing DNA ligation and leading to lethal double-strand breaks and mitochondrial dysfunction. Because cancer cells often exhibit increased mitochondrial biogenesis and reliance on TOP1MT for mtDNA maintenance, this complex represents a strategic target for inducing apoptosis in malignant cells. Research indicates that TOP1MT deficiency can sensitize cells to DNA-damaging agents, highlighting its role in cellular stress responses and its potential as a synergistic therapeutic target.

Other names

Mitochondrial topoisomerase IDNA topoisomerase I, mitochondrialTOP1MT-DNA cleavage complexTopoisomerase (DNA) I, mitochondrial

Stabilization of the covalent topoisomerase I-DNA cleavage complex, preventing DNA religation and inducing mitochondrial DNA damage.